Broadly neutralizing antibodies to HIV will likely be needed if any AIDS vaccine is to prevent people from becoming infected with HIV. Most of the AIDS vaccine candidates now entering clinical trials are aimed at stimulating certain infection-fighting white blood cells, not antibodies. While these vaccines may prevent people who become infected with HIV from progressing to AIDS, they are not likely to prevent an infection in the first place. To do that, neutralizing antibodies against HIV-1 will likely be needed as well.
Given the potential anti-viral effects of neutralizing antibodies, it is not unexpected that HIV-1 has evolved multiple mechanisms to protect it from antibody binding including, for example, the heavy glycosylation of the envelope polypeptide, the trimerization of the gp120 and gp41 structure which can shield antibody access to the underlying peptide structure, and the kinetics and spatial constraints that impede antibodies from binding potentially vulnerable sites during receptor binding and membrane fusion. However, despite all of the defense mechanisms of HIV against neutralizing antibodies, primary isolates of HIV from different genetic subtypes can be neutralized by some broadly reactive human monoclonal antibodies such as b12, 2G12, 2F5, Z13, and 4E10. In addition, a few rare sera from HIV-1 infected individuals have broad neutralizing activity. The existence of such broadly neutralizing antibodies provides an indication that a vaccine inducing neutralizing antibodies can indeed be created.
Methods and compositions are needed in the art which provide immunogens that elicit neutralizing antibodies against HIV-1.